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Chapter 17
Lecture
Outline
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Chapter 17 Outline
Structure
and Function of the Kidney
Glomerular Filtration
Reabsorption of Salt and Water
Renal Plasma Clearance
Renal Control of Electrolyte and Acid-Base Balance
Clinical Applications
17-2
Kidney Function
Is
to regulate plasma and interstitial fluid by formation
of urine
In process of urine formation, kidneys regulate:
Volume of blood plasma, which contributes to BP
Waste products in plasma
Concentration of electrolytes
Including Na+, K+, HCO3-, and others
Plasma pH
17-3
Gross Structure of the Urinary
System
17-4
Structure of Urinary System
Paired
kidneys are
on either side of
vertebral column
below diaphragm
About size of fist
Urine flows from
kidneys into ureters
which empty into
bladder
Urethra drains urine
from bladder
17-5
Structure of Kidney
 Cortex
contains many capillaries and outer parts of nephrons
 Medulla consists of renal pyramids separated by renal columns
 Pyramid contains minor calyces which unite to form a major
calyx
17-6
Structure of Kidney continued
 Major
calyces join
to form renal pelvis
which collects urine
 Conducts urine
to ureters which
empty into
bladder
17-7
Micturition Reflex (Urination)
Bladder
has a smooth muscle wall called the detrussor
muscle
Stretch can cause spontaneous Act. Pots. and
contraction
Also innervated and controlled by parasympathetic
Drugs for overactive bladders target muscarinic
ACh receptors
17-8
Micturition Reflex (Urination) continued
Actions
of internal and external urethral sphincters are
regulated by reflex center located in sacral part of cord
Filling of bladder activates stretch receptors that send
impulses to micturition reflex center
This activates Parasymp neurons causing
contraction of detrusor muscle that relaxes internal
urethral sphincter creating sense of urgency
There is voluntary control over external urethral
sphincter
When urination is consciously initiated, descending
motor tracts to micturition center inhibit somatic motor
fibers of external urethral sphincter and urine is
expelled
17-9
Microscopic Structure of the Kidney
17-10
Nephron
 Is
functional unit of kidney; responsible for forming urine
 >1 million nephrons/kidney
 Consists of small tubes and associated small blood vessels
17-11
Renal Blood Vessels
Blood
enters kidney
through renal artery
Which divides
into interlobar
arteries
That divide
into arcuate
arteries that
give rise to
interlobular
arteries
17-12
Renal Blood Vessels continued
Interlobular
arteries give rise to afferent arterioles
which supply glomeruli
Glomeruli are mass of capillaries inside glomerular
capsule that gives rise to filtrate that enters nephron
tubule
Efferent arteriole drains glomerulus and delivers that
blood to peritubular capillaries (vasa recta)
Blood from peritubular capillaries enters interlobular
veins
17-13
17-14
Nephron Tubules
 Tubular
part of nephron begins with glomerular capsule which
transitions into proximal convoluted tubule (PCT), then to
descending and ascending limbs of Loop of Henle (LH), and
distal convoluted tubule (DCT)
 Tubule ends where it empties into collecting duct (CD)
17-15
Glomerular (Bowman's) Capsule
Surrounds
glomerulus
Together they
form renal
corpuscle
Is where glomerular
filtration occurs
Filtrate passes
into proximal
convoluted tubule
17-16
Proximal Convoluted Tubule
Walls
consist of single layer of cuboidal cells with
millions of microvilli
Which increase surface area for reabsorption
During reabsorption, salt, water, and other
molecules needed by the body are transported from
the lumen through the tubular cells and into
surrounding peritubular capillaries
17-17
Type of Nephrons
 Cortical
nephrons
originate in outer 2/3
of cortex
 Juxtamedullary
nephrons originate
in inner 1/3 cortex
 Have long LHs
 Important in
producing
concentrated
urine
17-18
Glomerular Filtration
17-19
Glomerular Filtration
Glomerular
capillaries and Bowman's capsule form a
filter for blood
Glomerular Caps are fenestrated--have large pores
between its endothelial cells
Big enough to allow any plasma molecule to pass
100-400 times more permeable than other Caps
17-20
Glomerular Filtration continued
To
enter tubule
filtrate must
pass through
narrow slit
diaphragms
formed
between
pedicels (foot
processes) of
podocytes of
glomerular
capsule
17-21
Glomerular Filtration continued
Plasma
proteins are mostly excluded from the filtrate
because of large size and negative charge
The slit diaphragms are lined with negative charges
which repel negatively-charged proteins
Some protein (especially albumin) normally enters
the filtrate but most is reabsorbed by receptormediated endocytosis
Defects in the slit diaphragm results in massive
leakage of proteinin the filtrate and thus appears
in the urine (=proteinuria)
17-22
Scanning electron micrograph of glomerular caps and capsule
17-23
An electron micrograph of the filtration barrier between the cap lumen & glomer. capsule
17-24
The Formation of Glomerular Ultrafiltrate
Only
a fraction
of plasma
proteins (green)
are filtered
Smaller plasma
solutes (purple)
easily enter the
glomerular
ultrafiltrate
17-25
Glomerular Filtration Rate (GFR)
Is
volume of filtrate produced by both kidneys/min
Averages 115 ml/min in women; 125 ml/min in men
Totals about 180L/day (45 gallons)
So most filtered water must be reabsorbed or
death would ensue from water lost through
urination
17-26
Regulation of GFR
Is
controlled by extrinsic and intrinsic (autoregulation)
mechanisms
Vasoconstriction or dilation of afferent arterioles affects
rate of blood flow to glomeruli and thus GFR
17-27
Sympathetic Effects
Sympathetic
activity constricts
afferent arteriole
Helps
maintain BP
and shunts
blood to heart
and muscles
17-28
Renal Autoregulation
Defined
as the ability of kidneys to maintain relatively
constant GFR in the face of fluctuating B.P.
2 mechanisms responsible:
Myogenic constriction of afferent arteriole due to
smooth muscle responding to an inc. in arterial
pressure
Achieved via effects of locally produced chemicals on
afferent arterioles part of tubuloglomerular feedback
17-29
17-30
Renal Autoregulation continued
Is
also maintained by negative feedback between
afferent arteriole and volume of filtrate
(tubuloglomerular feedback)
Increased flow of filtrate sensed by macula densa
(part of juxtaglomerular apparatus) in thick
ascending LH
Signals afferent arterioles to constrict
17-31
Reabsorption of Salt and Water
17-32
Reabsorption of Salt and H2O
In
PCT returns most molecules and H2O from filtrate
back to peritubular capillaries
About 180 L/day of ultrafiltrate produced; only 1–2 L
of urine excreted/24 hours
Urine volume varies according to needs of body
Minimum of 400 ml/day urine necessary to
excrete metabolic wastes (obligatory water loss)
17-33
Reabsorption of Salt and H2O continued
 The
transport of
molecules out of the
tubular filtrated back
into the blood =
reabsorption
 Water is never
transported
 Other molecules
are transported
and water follows
by osmosis
17-34
The Mech. of Reabsorption in the proximal tubule
 There
is coupled
transport of glucose and
Na+ into the cytoplasm &
 Primary active transport
of Na+ across basolateral
membrane by Na+/K+
pump
 Glucose is then
transported out of cell by
facilitated diffusion and is
reabsorbed into the blood
17-35
Salt and water reabsorption in the proximal tubules:
17-36
Significance of PCT Reabsorption
Na+, Cl-, and H2O is reabsorbed in PCT and
returned to bloodstream
An additional 20% is reabsorbed in descending loop of
Henle
Thus 85% of filtered H2O and salt are reabsorbed early
in tubule
This is constant and independent of hydration levels
Energy cost is 6% of calories consumed at rest
The remaining 15% is reabsorbed variably,
depending on level of hydration
~65%
17-37
Concentration Gradient in Kidney
In
order for H2O to be reabsorbed, interstitial fluid must
be hypertonic
Osmolality of medulla interstitial fluid (1200-1400
mOsm) is 4X that of cortex and plasma (300 mOsm)
This concentration gradient results largely from loop
of Henle which allows interaction between
descending and ascending limbs
17-38
The Countercurrent Multiplier System
 Extrusion
of NaCl from
ascending limb makes
surrounding interstitial
fluid more concentrated
 Multiplication of concent.
due to descend. limb
passively permeable to
water—causing fluid to
inc. in concent. as the
surrounding interstitial
fluid more concent.
 Deepest region of
medulla at 1,400mOsm
17-39
Ascending Limb Loop of Henle


Has a thin segment in
depths of medulla and
thick part toward cortex
Impermeable to H2O;
permeable to salt; thick
part Actively Transports
salt out of filtrate
 Active Transport of salt
causes filtrate to
become dilute (100
mOsm) by end of Loop
of Henle
17-40
The Transport of Ions in the Ascending Limb
 In
thick segment,
Na+ and K+ together
with 2 Cl- enter
tubule cells
 Na+ then actively
transported out into
interstitial space and
Cl- follows passively
 K+ diffuses back into
filtrate; some also
enters interstitial
space
17-41
AT in Ascending Limb LH continued
 Na+
is Actively
Transported across
basolateral
membrane by Na+/ K+
pump
 Cl- passively follows
Na+ down electrical
gradient
 K+ passively diffuses
back into filtrate
17-42
Countercurrent Multiplier System
 Countercurrent
flow and proximity allow descending and
ascending limbs of Loop of Henle to interact in way that causes
osmolality to build in medulla
 Salt pumping in thick ascending part raises osmolality around
descending limb, causing more H2O to diffuse out of filtrate
 This raises osmolality of filtrate in descending limb which
causes more concentrated filtrate to be delivered to
ascending limb
 As this concentrated filtrate is subjected to Active Transport
of salts, it causes even higher osmolality around descending
limb (positive feedback)
 Process repeats until equilibrium is reached when osmolality
of medulla is 1400
17-43
Countercurrent Exchange in Vasa Recta
 Is
important component of
countercurrent multiplier
 Permeable to salt, H2O (via
aquaporins), and urea
 Recirculates salt, trapping
some in medulla interstitial
fluid
 Reabsorbs H2O coming out
of descending limb
 Descending section has
urea transporters
 Ascending section has
fenestrated capillaries
17-44
The Role of Urea in Urine Concentration
 Urea
diffuses out of
inner collect. duct
into interstitial fluid
in medulla
 Urea then passes
into ascend. limb so
it recirculates in
interstitial fluid in
medulla
 Water is reabsorbed
by osmosis from
collect. duct
17-45
17-46
Collecting Duct (CD)
Plays
important role in water conservation
Is impermeable to salt in medulla
Permeability to H2O depends on levels of ADH
17-47
Homeostasis of Plasma Concent.
Maintained by ADH
 Is
secreted by post
pituitary in response to
dehydration
 Stimulates insertion of
aquaporins (water
channels) into plasma
membrane of Collect.
Duct
 When ADH is high, H2O
is drawn out of CD by
high osmolality of
interstitial fluid
 And reabsorbed by
vasa recta
17-48
Osmolality of Different Regions of the Kidney
17-49
Renal Plasma Clearance
17-50
Secretion is the Opposite of Reabsorption
The
active transport of substances from the peritubular
capillaries into the tubular fluid = secretion
Secretion is opposite in direction to that which occurs
in reabsorption
Reabsorption decreases renal clearance; secretion
increases renal clearance
17-51
Renal Clearance
Excretion
rate =
(filtration rate + secretion rate) - reabsorption rate
17-52
Tubular Secretion of Drugs
 Many
drugs, toxins, and metabolites are secreted by membrane
transporters in the Proximal Tubule
 Major group of transporters involved is organic anion
transporter (OAT)
 Eliminate xenobiotics, therapeutic and abused drugs
 Located in basolateral membrane of prox. Tubule
 Larger xenobiotics elimin. by OATS in liver that transport into
bile
 Also some organic cation transporters that eliminate particular
xenobiotics, such as nicotine
 Considered polyspecific—overlapping specificity
17-53
Inulin Measurement of GFR
 Inulin,
a fructose polymer, is useful for measuring GFR because
is neither reabsorbed or secreted
 Rate at which a substance is filtered by the glomeruli can be
calculated:
 Quantity filtered = GFR x P
 P = inulin concentration in plasma
 Quantity excreted (mg/min) = V x U
 V = rate of urine formation in ml/min; U = inulin concentration
in urine in mg/ml
 Amount filtered = amount excreted
GFR(ml/min) = V(ml/min) x U(mg/ml)
P(mg/ml)
17-54
Renal Clearance of Inulin
17-55
Renal Plasma Clearance (RPC)
 Is
volume of plasma from which a substance is completely
removed/min by excretion in urine
 If substance is filtered but not reabsorbed then all filtered will be
excreted RPC = GFR
 If substance is filtered and reabsorbed then RPC < GFR
 If substance is filtered but also secreted and excreted then RPC
will be > GFR (=120 ml/ min)
RPC = V x U
P
V= urine volume/min
U= concent. of subst. in urine
P = concent. of subst. in plasma
17-56
Clearance of Urea
 Urea
is freely filtered into glomerular capsule
 Urea clearance calculations demonstrate how kidney handles a
substance: RPC = V X U/P
 V = 2ml/min; U = 7.5 mg/ml of urea; P = 0.2 mg/ml of urea
 RPC = (2ml/min)(7.5mg/ml)/(0.2mg/ml) = 75ml/min
 Urea clearance is 75 ml/min, compared to clearance of inulin
(120 ml/min)
 Thus 40-60% of filtered urea is always reabsorbed
 Is passive process because of presence of carriers for
facilitative diffusion of urea
17-57
Measurement of Renal Blood Flow
Not
all blood delivered to glomerulus is filtered into
glomerular capsule
20% is filtered; rest passes into efferent arteriole
and back into circulation
Substances that aren't filtered can still be cleared by
active transport (secretion) into tubules
17-58
Total Renal Blood Flow Using PAH
 PAH
clearance is used to measure total renal blood flow
 Normally averages 625 ml/min
 It is totally cleared by a single pass through a nephron
 So it must be both filtered and secreted
 Filtration and secretion clear only molecules dissolved in
plasma
 To get total renal blood flow, amount of blood occupied by
erythrocytes must be taken into account
 45% blood is RBCs; 55% is plasma
  total renal blood flow = PAH clearance
 = 625/0.55 = 1.1L/min
0.55
17-59
Total Renal Blood Flow Using PAH continued
17-60
Glucose and Amino Acid Reabsorption
Filtered
glucose and amino acids are normally 100%
reabsorbed from filtrate
Occurs in Proximal Tubule by carrier-mediated
cotransport with Na+
Transporter displays saturation if ligand
concentration in filtrate is too high
 Level needed to saturate carriers and achieve
maximum transport rate is transport maximum
(Tm)
Glucose and amino acid transporters don't saturate
under normal conditions
17-61
Glycosuria
Is
presence of glucose in urine
Occurs when glucose > 180-200mg/100ml plasma
(= renal plasma threshold)
Glucose is normally absent because plasma levels
stay below this value
Hyperglycemia has to exceed renal plasma
threshold
Diabetes mellitus occurs when hyperglycemia
results in glycosuria
17-62
Renal Control of Electrolyte and
Acid-Base Balance
17-63
Electrolyte Balance
regulate levels of Na+, K+, H+, HCO3-, Cl-, and
PO4-3 by matching excretion to ingestion
Control of plasma Na+ is important in regulation of
blood volume and pressure
Control of plasma of K+ is important in proper function
of cardiac and skeletal muscles
Kidneys
17-64
Role of Aldosterone in Na+/K+ Balance
filtered Na+ and K+ reabsorbed before Distal Tub.
Remaining is variably reabsorbed in Distal Tub. and
cortical Collect. Duct according to bodily needs
Regulated by aldosterone (controls K+ secretion
and Na+ reabsorption)
In the absence of aldosterone, 80% of remaining
Na+ is reabsorbed in Distal Tub. and cortical
Collect. Duct
When aldosterone is high all remaining Na+ is
reabsorbed
90%
17-65
K+ is Reabsorbed and Secretion
 K+
almost
completely
reabsorbed in prox.
tubule
 Under aldosterone
stim. secreted into
cortical collect.
Ducts
 All K+ in urine from
secretion rather
than filtration
17-66
Juxtaglomerular Apparatus (JGA)
Is
specialized region in each nephron where afferent
arteriole comes in contact with thick ascending limb LH
17-67
Renin-Angiotensin-Aldosterone System
Is
activated by release of renin from granular cells
within afferent arteriole
Renin converts angiotensinogen to angiotensin I
Which is converted to Angio II by angiotensinconverting enzyme (ACE) in lungs
Angio II stimulates release of aldosterone
17-68
Regulation of Renin Secretion
Inadequate
intake of NaCl always causes decreased
blood volume
Because lower osmolality inhibits ADH, causing less
H2O reabsorption
Low blood volume and renal blood flow stimulate
renin release
Via direct effects of BP on granular cells and by
Symp activity initiated by arterial baroreceptor
reflex
17-69
17-70
Macula Densa
 Located
where
tubule cells make
contact with
granular cells
 Acts as sensor for
tubuloglomerular
feedback; needed
for autoreg. of GFR
 Signals afferent
arteriole to
constrict
 Signals granular
cells to dec.
secretion of renin
when blood Na+
is inc.
17-71
17-72
Atrial Natriuretic Peptide (ANP)
Is
produced by atria due to stretching of walls
An aldosterone antagonist
Stimulates salt and H2O excretion
Acts as an endogenous diuretic
17-73
Relationship Between Na+, K+, and H+
17-74
The Reabsorption of Na+ and Secretion of K+
 In
distal tubule, K+ and
H+ secreted in
response to potential
difference prod. By
reabsorption of Na+
 High
concent. of H+
may therefore dec. K+
secretion, and vice
versa
17-75
Renal Acid-Base Regulation
help regulate blood pH by excreting H+ and/or
reabsorbing HCO3Most H+ secretion occurs across walls of Proximal
Tub. in exchange for Na+ (Na+/H+ antiporter)
Normal urine is slightly acidic (pH = 5-7) because
kidneys reabsorb almost all HCO3- and excrete H+
Kidneys
17-76
Reabsorption of HCO3- in PCT
Is
indirect because apical membranes of PCT cells are
impermeable to HCO3When urine acidic, bicarbonate combines with H+ to
form carbonic acid
Carbonic acid in filtrate is converted to carbon dioxide
and water in a reaction catalyzed by carbonic
anhydrase (located in apical cell memb. of proximal
tubule in contact with filtrate)
17-77
Reabsorption of HCO3- in PCT continued
urine is acidic, HCO3- combines with H+ to form H2CO3
(catalyzed by CA on apical membrane of PCT cells)
 H2CO3 dissociates into CO2 + H2O
 CO2 diffuses into PCT cell and forms H2CO3 (catalyzed by CA)
 H2CO3 splits into HCO3- and H+ ; HCO3- diffuses into blood
 When
17-78
Urinary Buffers
Nephron
cannot produce urine with pH < 4.5
Excretes more H+ by buffering H+s with HPO4-2 or NH3
before excretion
Phosphate enters tubule during filtration
Ammonia produced in tubule by deaminating amino
acids
Buffering reactions
 HPO4-2 + H+  H2PO4 NH3 + H+  NH4+ (ammonium ion)
17-79
Clinical Applications
17-80
Diuretics
 Are
used to lower blood volume because of hypertension,
congestive heart failure, or edema
 Increase volume of urine by increasing proportion of glomerular
filtrate that is excreted
 Loop diuretics are most powerful; inhibit AT salt in thick
ascending limb of LH
 Thiazide diuretics inhibit NaCl reabsorption in 1st part of DCT
 Carbonic anhydrase inhibitors prevent H2O reabsorption in PCT
when HCOs- is reabsorbed
 Osmotic diuretics increase osmotic pressure of filtrate
17-81
Sites of Action of Clinical Diuretics
17-82
Kidney Diseases
In
acute renal failure, ability of kidneys to excrete
wastes and regulate blood volume, pH, and
electrolytes is impaired
Rise in blood creatinine and decrease in renal
plasma clearance of creatinine
Can result from atherosclerosis, inflammation of
tubules, kidney ischemia, or overuse of NSAIDs
17-83
Kidney Diseases continued
Glomerulonephritis
is inflammation of glomeruli
Autoimmune attack against glomerular capillary
basement membranes
Causes leakage of protein into urine resulting in
decreased colloid osmotic pressure and resulting
edema
17-84
Kidney Diseases continued
 In
renal insufficiency, nephrons have been destroyed as a result
of a disease
 Clinical manifestations include salt and H2O retention and
uremia (high plasma urea levels)
 Uremia is accompanied by high plasma H+ and K+ which
can cause uremic coma
 Treatment includes hemodialysis
 Patient's blood is passed through a dialysis machine
which separates molecules on basis of ability to diffuse
through selectively permeable membrane
 Urea and other wastes are removed
17-85